Objective To evaluate the rehabilitation efficacy of moderate intensity aerobic exercise on patients with chronic obstructive pulmonary disease (COPD)-obstructive sleep apnea (OSA) overlap syndrome. Methods A retrospective cohort study was used in the study. The patients who were diagnosed with COPD-OSA overlap syndrome and applied positive airway pressure (PAP) from January 2021 to December 2023 were selected in the Department of Respiratory Rehabilitation, at the Fourth Rehabilitation Hospital of Shanghai. A total of 29 patients [aged (62.2±5.9) years, male 65.5%] with overlap syndrome received moderate intensity aerobic training for 20 weeks were enrolled as the intervention group (IG). At the same time, 29 patients [(64.6±6.9) years, male 62.1%] with overlap syndrome who didn’t receive aerobic training were selected as the control group (CG). The differences in motor function, daily living abilities, body composition, respiratory function, psychological state and sleep parameters between two cohorts of patients before and after treatment were compared. Results After 20 weeks of aerobic exercise, the various parameters of IG demonstrated significant improvement compared with those before treatment: a notable increase in the 6 min walk distance (6MWD) [(268.62±47.02) m vs (316.97±58.44) m], quadriceps muscle strength [22.40 (20.40, 27.45) kg vs 25.40 (20.00, 30.45) kg], Barthel index (BI) scores [(66.03±12.42) vs (76.72±11.82)], a reduction in the 5 times sit-to-stand test (5TSTS) [19.50 (15.94, 31.10) s vs 13.50 (11.75, 18.50) s], body mass index (BMI) [(25.16±3.17) kg/m² vs (22.31±2.16) kg/m²] and fat mass (FM) [(24.13±9.22) kg vs (20.47±8.32) kg]. Additionally, there were significant enhancements observed in PSG parameters, blood gas analysis results, Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) scores after training in IG (all P<0.05). In contrast, the CG exhibited improvements in quadriceps muscle strength and the modified Medical Research Council (mMRC) as well as PSG parameters and psychological state; while there was an FM increase in this group (all P<0.05). Compared with the CG, the 6MWD [(316.97±58.44) m vs 239.93±37.80) m], quadriceps muscle strength [25.40 (20.00, 30.45) kg vs 23.70 (20.50, 25.60) kg], 5TSTS [13.50 (11.75, 18.50) s vs 19.50 (17.60, 23.12) s], BI [(76.72±11.82) vs （67.59±10.74)], mMRC, pH, PaO₂, TS90%, BMI [(22.31±2.16) kg/m² vs（26.17±3.83) kg/m²], FM, HAMD, HAMA of the IG patients showed significant improvement (all P<0.05). However, there were no significant differences observed between the two groups in terms of percentage of predicted forced expiratory volume in one second (FEV₁%） (43.72%±9.49% vs 43.97%±7.22%), PaCO₂, apnea hypopnea index, pulse oxygen saturation （L-SpO₂）%, fat free mass and fat free mass index (P>0.05). Conclusions The combination of a 20-week moderate-intensity aerobic training and PAP demonstrates significant improvements in motor function, reduction in body fat, alleviation of hypoxia and respiratory difficulties, enhancement of psychological state and daily life abilities. This intervention may be considered suitable for patients with COPD-OSA overlap syndrome.